3MW1
p38 kinase Crystal structure in complex with small molecule inhibitor
Summary for 3MW1
| Entry DOI | 10.2210/pdb3mw1/pdb |
| Related | 3HRB |
| Descriptor | Mitogen-activated protein kinase 14, 8-(2,6-dichlorophenyl)-4-(2,4-difluorophenyl)-2-piperidin-4-yl-1,7-naphthyridine 7-oxide (3 entities in total) |
| Functional Keywords | p38 map kinase, transferase, inhibitor complex, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm (By similarity): Q16539 |
| Total number of polymer chains | 1 |
| Total formula weight | 41698.34 |
| Authors | Segarra, V.,Caturla, F.,Lumeras, W.,Roca, R.,Fisher, M.,Lamers, M. (deposition date: 2010-05-05, release date: 2011-04-27, Last modification date: 2023-11-01) |
| Primary citation | Lumeras, W.,Vidal, L.,Vidal, B.,Balague, C.,Orellana, A.,Maldonado, M.,Dominguez, M.,Segarra, V.,Caturla, F. 1,7-Naphthyridine 1-Oxides as Novel Potent and Selective Inhibitors of p38 Mitogen Activated Protein Kinase J.Med.Chem., 54:7899-7910, 2011 Cited by PubMed Abstract: The design, synthesis, and ability to inhibit p38α MAP kinase by a novel series of naphthyridine N-oxides will be described. Some of these compounds showed a significant reduction in the LPS-induced TNFα production in human whole blood. Structure-activity relationship studies revealed that N-oxide oxygen was essential for activity and was probably a determinant factor for its marked selectivity against other related kinases. After an extensive SAR exercise, several compounds from this series were identified as very potent p38α inhibitors. In vivo efficacy of some derivatives was demonstrated to reduce TNFα levels in an acute murine model of inflammation (ED(50) = 0.5 mg/kg in LPS-induced TNFα production when dosed orally 1.5 h prior to LPS administration). The oral efficacy was further demonstrated in a chronic model of adjuvant arthritis in rats with established disease when administered orally (ED(50) < 1 mg/kg). PubMed: 21999461DOI: 10.1021/jm200975u PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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